The production of a high density mouse linkage map is one of the major goals of the effort to characterize the mammalian genome. These mapping studies have received increased impetus from the Human Genome Initiative which considers the mouse to be an important model system. Our mapping efforts until recently have been restricted to the analysis of Chinese hamster x mouse somatic cell hybrids by Southern blotting to assign newly identified genes to specific chromosomes. We have now expanded these studies to include analysis of two genetic crosses, an interspecies and an intersubspecies backcross. DNAs from the progeny of these crosses have been typed for a variety of polymorphic reference loci to permit mapping of unknown markers to specific positions on the linkage map. These studies have resulted in the chromosomal mapping of a large number of genes including the polymerase B gene, a gene involved in spermatogenesis, several protein kinase genes, various enzymes, and genes of unknown function with specific patterns of tissue expression. Several of these latter genes map at or near known mouse mutations and therefore are potential candidates for these mutations. Thus, two genes specifically expressed in cerebellum map at or near the neurological mutations nervous and weaver, the vitamin K receptor maps to the same chromosome as the gene for warfarin resistance, and a brain cDNA which appears to encode a transmembrane protein maps at or near the grey tremor locus. These genes and their expression are now being characterized in the mutant mice.